as-601245 and Breast-Neoplasms

It has been reported that supplementation with high-dose vitamin B(6) (B(6)) exerts antitumor effects in rodent models of cancer. However, the mechanism of these effects remains poorly understood. High-dose B(6) also suppresses cell proliferation and induces apoptosis of human breast adenocarcinoma MCF-7 cells. Based on preliminary experiments using DNA microarray analyses, we hypothesized that high-dose pyridoxine (PN) might induce IGF-binding protein-3 (IGFBP-3) expression in MCF-7 cells. In this study, we investigated IGFBP-3 induction by 3 or 10 mM PN using a quantitative real-time PCR method. We found that the induction reached a maximum of 24-fold with 10 mM PN for 72 h compared with non-treated cells. The induction of IGFBP-3 by PN was inhibited by a p53-specific inhibitor, pifithrin-α, in a dose-dependent manner, but was not affected by PD169316 (MAPK inhibitor), AS601245 (c-Jun N-terminal kinase inhibitor) or SL327 (MEK1/2 inhibitor). High-dose PN did not induce p53 mRNA expression. The IGFBP-3 induction by PN seemed to be related to p53 activation.

Topics: Acetonitriles; Antineoplastic Agents; Apoptosis; Benzothiazoles; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Dietary Supplements; Dose-Response Relationship, Drug; Female; Gene Expression; Humans; Imidazoles; Insulin-Like Growth Factor Binding Protein 3; Mitogen-Activated Protein Kinases; Oligonucleotide Array Sequence Analysis; Pyridoxine; Real-Time Polymerase Chain Reaction; RNA, Messenger; Toluene; Tumor Suppressor Protein p53; Vitamin B Complex